A Study to Determine the Clinical Safety/Tolerability and Exploratory Efficacy of EHT 0202 as Adjunctive Therapy to Acetylcholinesterase Inhibitor in Mild to Moderate Alzheimer's Disease

NCT00880412 | Completed Phase 2 DMC

• 1 other identifier: EHT0202/002
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 22

Brief Summary

The objective of this 3-month study is to assess the safety and efficacy of EHT 0202 in addition to acetylcholinesterase inhibitor in patients suffering from Alzheimer's Disease.

Conditions

Alzheimer's Disease

Keywords

safety; efficacy; Alzheimer's disease; treatment; phase II; study; cholinesterase inhibitor

Outcome Measures

Primary Outcomes (1)

• incidence/frequency and severity of adverse events, relation to treatment start and drug exposure, drop-out rate, including reason for withdrawal, clinical examination, change from screening of biological safety parameters, vital signs, ECG and weight.

  all study visits

Secondary Outcomes (1)

• Assessment of cognition (ADAS-Cog, Neuropsychological Test Battery, MMSE), patient's global functioning (CDR-SB,CGI), patient's behaviour (NPI), daily living activities (ADCS-ADL) and caregiver's burden. Population PK of EHT 0202 and PK/PD profile.

  at the end of the 3-month study treatment period

Study Arms (3)

EHT 0202 40 mg bid

EXPERIMENTAL

study treatment is given in addition to one acetylcholinesterase inhibitor (galantamine, rivastigmine or donepezil)

Drug: EHT 0202 etazolate

EHT 0202 80 mg bid

EXPERIMENTAL

study treatment is given in addition to one acetylcholinesterase inhibitor (galantamine, rivastigmine or donepezil)

Drug: EHT 0202 etazolate

placebo bid

PLACEBO COMPARATOR

study treatment is given in addition to one acetylcholinesterase inhibitor (galantamine, rivastigmine or donepezil)

Drug: Placebo

Interventions

EHT 0202 etazolate DRUG

In each arm, 2 capsules of study treatment (capsules of EHT0202 40mg and/or placebo) are taken twice a day during breakfast and dinner over a 3-month treatment period. There is non treatment adjustment.

Also known as: EHT 0202, etazolate

EHT 0202 40 mg bid; EHT 0202 80 mg bid

Placebo DRUG

In each arm, 2 capsules of study treatment (capsules of EHT0202 40mg and/or placebo) are taken twice a day during breakfast and dinner over a 3-month treatment period. There is non treatment adjustment.

placebo bid

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory male or female patient, aged 60-90 years old included at screening, and living at home.
• Patient having a clinical diagnosis of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
• Mild to moderate AD with a MMSE total score ≥ 12 and ≤ 24 at screening.
• Written informed consent obtained from the patient or, if appropriate, from legal representative according to local laws and regulations. The caregiver will also have to sign a specific informed consent form regarding his/her participation in the study.
• Patient treated for AD treatment with one AChEI (donepezil, galantamine, or rivastigmine), according to the recommended posology mentioned in the summary of product characteristics, for at least 3 months and with a stable dose for at least 2 months prior to screening. The dose should be kept unchanged throughout the study duration.
• Patient with a cerebral CT-scan or cerebral MRI compatible with AD diagnosis, with no brain lesions that may be related to another diagnosis and that could be responsible for the current patient's condition (ex, but not limited to, non-AD dementia, brain injury, brain tumour, stroke, normal pressure hydrocephalus,…). A cerebral CT-scan or cerebral MRI has to be performed and results have to be available prior patient's randomization if the results of the brain imagery performed to settle the AD diagnosis are not available in the patient's file. Brain imaging has also to be performed if considered necessary by the investigator, such as in case of emerging neurological symptoms or in case of worsening of existing neurological symptoms.
• Neurological exam without any particularities or without any specific focal signs likely to be related to other conditions than AD.
• No contra-indication to AChEI treatment and absence of significant adverse events considered to be related to AChEI treatment at screening and randomisation.
• Patient and patient's caregiver able to comply with study procedures, notably regarding the drug intake at the end of the meal which has to be supervised by the caregiver or another competent person.

You may not qualify if:

• Diagnosis of vascular dementia according to NINDS-AIREN criteria, or other non-AD dementia, or CNS pathology (including but not limited to brain injury, brain tumour, stroke, normal pressure hydrocephalus, Parkinson's disease, epilepsy,multiple sclerosis,…) that may be responsible for dementia.
• Clinically significant pathology and/or uncontrolled condition, including but not limited to cancer, infectious (like AIDS), gastro-intestinal, hepatic, renal, respiratory, endocrine(like diabetes mellitus, thyroiditis) pathology.
• History or current clinically significant psychiatric pathology (including but not limited to psychotic disorders, bipolar disorder, personality disorders) that may interfere with study assessments.
• Current major depressive disorder, either treated or not, associated with clinically significant symptoms.
• Low blood level of vitamin B12, TSH levels out of normal range at screening.
• Current forbidden medication intake or intake within 2 weeks prior to screening.
• History or presence of clinically conditions that may interfere with product metabolism or with study assessments.
• Systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 90 mmHg at screening and/or randomisation.
• QTc interval (Bazett's correction) ≥ 430 msec for male and ≥ 450 msec for female at screening.
• Laboratory values (biochemistry, haematology, urinalysis) considered as clinically significant and/or that may interfere with study assessments, according to the investigator.
• ALAT, ASAT, ALP \> 2.5 times the upper normal limit (UNL), total bilirubin \> 1.5 UNL or history of significant liver pathology including hepatitis caused by drugs, HBV, HCV.
• BUN, creatinin \> 1.5 UNL.
• Current or recent history of drug or alcohol abuse or dependence.
• Patient not registered at "Sécurité Sociale".
• Participation in another study within 1 month prior to screening and during the whole duration of the study.

Sponsors & Collaborators

• Exonhit: lead

Study Sites (22)

Hôpital Privé Les Magnolias

Ballainvilliers, 91160, France

Location

Cabinet Médical

Bergerac, 24100, France

Location

Fleyriat Hospital

Bourg-en-Bresse, 01012, France

Location

Cabinet Médical

Dijon, 21000, France

Location

Charles Foix Hospital

Ivry-sur-Seine, 94026, France

Location

Cabinet Médical

La Seyne-sur-Mer, 83500, France

Location

Roger Salengro Hospital

Lille, 59037, France

Location

Dupuytren Hospital

Limoges, 87042, France

Location

Clinique Léopold Bellan

Magnanville, 78200, France

Location

Cabinet Médical

Montpellier, 34070, France

Location

Cabinet Médical 2

Montpellier, 34080, France

Location

CHU Nantes Hôpital Laennec

Nantes, 44093, France

Location

Cabinet Médical 2

Nice, 06000, France

Location

Cabinet Médical

Nice, 06000, France

Location

CHU Cochin Broca

Paris, 75013, France

Location

Cabinet Médical

Rambouillet, 78120, France

Location

CHU Rennes

Rennes, 35033, France

Location

Cabinet Médical

Rodez, 12000, France

Location

Cabinet Médical

Rueil-Malmaison, 92500, France

Location

Cabinet Médical

Saint-Brieuc, 22000, France

Location

Cabinet Médical

Toulon, 83000, France

Location

Purpan-Casselardit Hospital - University of Toulouse

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Etazolate

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Bruno Vellas, MD

  Casselardit Hospital - University of Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 10, 2009
• First Posted: April 13, 2009
• Study Start: April 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: August 1, 2009
• Last Updated: September 21, 2009

Record last verified: 2009-09

Locations

FR (22)